One of the standard treatments for aCRC is IRI-based regimens, which are commonly used as second line treatment in Japan. We conducted a prospective observational study to examine the correlation between UGT1A1 genotypes and the clinical outcome of IRI-based regimens in Japanese pts with aCRC (NCT 01039506). We presented previously the results of OS, the secondary endpoint (ASCO 2015, Abst No. 3525). Furthermore, We are going to present update results of OS (ASCO 2016, Abst No. 3571). We developed a nomogram for predicting survival of pts treated with second-line IRI-based regimens after first-line oxialiplatin-based treatment.
From Oct 2009 to Mar 2012, 1,376 pts with histologically confirmed aCRC treated with IRI-based regimens were enrolled into the study. Among all enrolled pts, 747 pts were treated with the second-line IRI-based regimens after first-line oxialiplatin-based treatment. A nomogram for predicting OS was developed using multivariable Cox proportional hazards model. The discriminative ability and predictive accuracy of the nomogram were determined by concordance index (c-index) and calibration plot. The nomogram was internally validated using bootstrap resampling.
The median OS was 18.5 months (95% CI, 16.8 – 20.7). The multivariable Cox proportional hazards model included age, performance status, resection of primary tumor, location of primary tumor (right vs left), tumor burden based on longitudinal diameters of target lesions according to the RECIST criteria, diabetes and white blood cell count as predictors of OS. The resulting nomogram demonstrated good discrimination and calibration in predicting OS, with a bootstrap-corrected c-index of 0.68. The nomogram showed good separation between risk groups stratified by tertile of the total score, with median OS of 10.1, 18.6, and 29.4 months for low, middle, and high risk groups, respectively.
This proposed nomogram is well calibrated and internally validated. External validation is essential before implementing this nomogram in clinical practice.
Clinical trial identification
NCT 01039506, first released on 23/Dec/2009. The trial protocol number is TOP009-061.
Legal entity responsible for the study
W. Ichikawa, S. Morita, Y. Ando, T. Sugiyama, Y. Ohashi: Advisory Board members of this study. Honoraria from Daiichi Sankyo. Y. Takii: Honoraria from Daiichi Sankyo. M. Arai: Employee of Daiichi sankyo. M. Sugihara: Employee of Daiichi Sankyo. Y. Sakata: Advisory Board members of this study. Honoraria from Daiichi Sankyo, Taiho Pharmaceutical, Yakult Honsya. All other authors have declared no conflicts of interest.